School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
J Drug Target. 2023 Mar;31(3):261-268. doi: 10.1080/1061186X.2022.2144869. Epub 2022 Nov 10.
The JNK pathway play a critical role in insulin resistance induced by a long-term high-sugar diet. However, the roles of up- and downstream molecules of the JNK pathway in insulin resistance are less known in vertebrates and invertebrates. As a classical organism in biological research, () has been widely applied to the studies of mechanism of insulin resistance. Based on previous studies, we found a novel predictive mechanism of the formation of insulin resistance in We found that JNK activated by high-sugar diet and dysregulated intestinal microbiota could mediate inflammation, and then the activated JNK released Upd3, which in turn stimulated Jak/STAT pathway to release ImpL2. ImpL2 can compete with insulin-like peptides (Dilps) for binding with the insulin receptor and inhibit the activation of insulin pathway. In this study, we reviewed novel studies on the insulin signalling pathway based on the model. The findings support our hypothesis. We, therefore, described how a long-term high-sugar diet disrupts intestinal microbiota to induce inflammation and the disruption of JNK-Jak/STAT axis. This description may offer some new clues to the formation of insulin resistance.
JNK 通路在长期高糖饮食诱导的胰岛素抵抗中发挥着关键作用。然而，JNK 通路上下游分子在脊椎动物和无脊椎动物中诱导胰岛素抵抗的作用尚不清楚。（）作为生物研究中的经典生物，已广泛应用于胰岛素抵抗机制的研究。基于之前的研究，我们发现了（）中胰岛素抵抗形成的一种新的预测机制。我们发现，高糖饮食激活的 JNK 和失调的肠道微生物群可以介导炎症，然后激活的 JNK 释放 Upd3，反过来刺激 Jak/STAT 通路释放 ImpL2。ImpL2 可以与胰岛素样肽（Dilps）竞争与胰岛素受体结合，从而抑制胰岛素通路的激活。在这项研究中，我们基于（）模型综述了胰岛素信号通路的新研究。研究结果支持我们的假设。因此，我们描述了长期高糖饮食如何破坏肠道微生物群诱导炎症和 JNK-Jak/STAT 轴的破坏。这一描述可能为胰岛素抵抗的形成提供了一些新的线索。
